UniProt Accession

 PRP8_HUMAN; Q6P2Q9; O14547; O75965 

Genbank Protein ID

 AF092565; AB007510; BC064370 

Genbank Nucleotide ID

 AAC61776.1; BAA22563.1; AAH64370.1 

Protein Name

 Pre-mRNA-processing-splicing factor 8 

Protein Synonyms/Alias

 220 kDa U5 snRNP-specific protein; PRP8 homolog; Splicing factor Prp8; p220 

Gene Name

 PRPF8 

Gene Synonyms/Alias

 PRPC8 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
29	PDYMSEEKLQEKARK	ubiquitination	[1, 2]
36	KLQEKARKWQQLQAK	ubiquitination	[3]
43	KWQQLQAKRYAEKRK	ubiquitination	[3]
68	MPPEHVRKIIRDHGD	ubiquitination	[3]
93	RVYLGALKYMPHAVL	ubiquitination	[1, 4, 5, 6, 7]
218	QPLRDSRKYVNGSTY	ubiquitination	[1, 3, 8]
267	LKAFFTSKALNMAIP	ubiquitination	[1, 2, 3, 4, 6, 9]
278	MAIPGGPKFEPLVRD	ubiquitination	[1, 2, 3, 4, 6, 8, 9, 10]
301	NEFNDINKIIIRQPI	ubiquitination	[1, 2, 11]
366	ISHRHSVKSQEPLPD	ubiquitination	[1, 2]
428	ALDIPLVKNWYREHC	ubiquitination	[1, 2, 3, 4, 6, 8, 9, 11]
442	CPAGQPVKVRVSYQK	ubiquitination	[3, 11]
449	KVRVSYQKLLKYYVL	ubiquitination	[1, 3, 4, 6]
452	VSYQKLLKYYVLNAL	ubiquitination	[3, 4, 6]
460	YYVLNALKHRPPKAQ	ubiquitination	[1, 3, 4, 6]
480	FRSFKATKFFQSTKL	ubiquitination	[1, 3, 4, 6]
511	LNLLIHRKNLNYLHL	ubiquitination	[3]
525	LDYNFNLKPVKTLTT	ubiquitination	[4, 6]
528	NFNLKPVKTLTTKER	ubiquitination	[3]
533	PVKTLTTKERKKSRF	ubiquitination	[1, 3]
555	REVLRLTKLVVDSHV	ubiquitination	[1, 3]
609	IRMCKDLKHLIYYRF	ubiquitination	[1, 3, 4, 6, 9, 11]
670	RHSKGVAKTVTKQRV	ubiquitination	[1]
674	GVAKTVTKQRVESHF	ubiquitination	[1]
702	DMMPEGIKQNKARTI	ubiquitination	[1, 2, 3, 4, 6, 8, 9]
705	PEGIKQNKARTILQH	ubiquitination	[3, 4, 6]
721	SEAWRCWKANIPWKV	ubiquitination	[3]
727	WKANIPWKVPGLPTP	ubiquitination	[1, 2, 3, 4, 6, 10]
746	ILRYVKAKADWWTNT	ubiquitination	[1, 3, 4, 6]
785	RLTRLYLKAEQERQH	ubiquitination	[1, 3, 4, 6, 8, 11]
833	PFPPLSYKHDTKLLI	ubiquitination	[3, 4, 6]
837	LSYKHDTKLLILALE	ubiquitination	[1, 3]
847	ILALERLKEAYSVKS	ubiquitination	[1, 3]
853	LKEAYSVKSRLNQSQ	ubiquitination	[1, 3]
932	YLWYEADKRRLFPPW	ubiquitination	[1, 2, 4, 6]
941	RLFPPWIKPADTEPP	ubiquitination	[1, 3]
983	MLESRFEKMYEKIDL	ubiquitination	[1, 3]
987	RFEKMYEKIDLTLLN	ubiquitination	[1, 3]
1012	IADYMTAKNNVVINY	ubiquitination	[1, 3]
1020	NNVVINYKDMNHTNS	ubiquitination	[1, 3, 4, 6]
1131	NIVGYNNKKCWPRDA	ubiquitination	[1, 2, 3, 4, 5, 6, 8]
1132	IVGYNNKKCWPRDAR	ubiquitination	[3, 7]
1144	DARMRLMKHDVNLGR	ubiquitination	[1, 3, 7]
1158	RAVFWDIKNRLPRSV	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 9]
1210	SYEEFTHKDGVWNLQ	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8]
1222	NLQNEVTKERTAQCF	ubiquitination	[1, 2, 3, 5, 7]
1290	ELLDLLVKCENKIQT	ubiquitination	[3, 5]
1294	LLVKCENKIQTRIKI	ubiquitination	[5]
1300	NKIQTRIKIGLNSKM	ubiquitination	[3]
1306	IKIGLNSKMPSRFPP	ubiquitination	[1, 2, 3]
1344	QSDLRWSKQTDVGIT	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 11]
1392	VWAEYALKRQEAIAQ	ubiquitination	[1, 2, 3, 4, 5, 6, 8, 11]
1425	RINTLFQKDRHTLAY	ubiquitination	[3]
1434	RHTLAYDKGWRVRTD	ubiquitination	[1, 3, 4, 6, 8, 9, 11]
1443	WRVRTDFKQYQVLKQ	ubiquitination	[1, 3, 4, 6, 11]
1449	FKQYQVLKQNPFWWT	ubiquitination	[2, 3, 4, 6, 9]
1463	THQRHDGKLWNLNNY	acetylation	[12]
1463	THQRHDGKLWNLNNY	ubiquitination	[1, 2, 3, 4, 6]
1505	WEGLFWEKASGFEES	ubiquitination	[1, 11]
1649	PSLLADSKDVMDSTT	ubiquitination	[1]
1732	LIQQAMAKIMKANPA	ubiquitination	[4, 6]
1735	QAMAKIMKANPALYV	ubiquitination	[3, 4, 6]
1792	VYRVTIHKTFEGNLT	ubiquitination	[4, 6]
1801	FEGNLTTKPINGAIF	ubiquitination	[4, 5, 6, 7]
1831	TSVWAGQKRLGQLAK	ubiquitination	[1, 2, 3, 5, 7]
1838	KRLGQLAKWKTAEEV	ubiquitination	[3]
1840	LGQLAKWKTAEEVAA	ubiquitination	[3, 7]
1859	LPVEEQPKQIIVTRK	ubiquitination	[1, 3, 4, 6]
1866	KQIIVTRKGMLDPLE	ubiquitination	[1, 3, 7]
1898	LPFQACLKVEKFGDL	ubiquitination	[3, 5, 7]
1901	QACLKVEKFGDLILK	ubiquitination	[3, 4, 6]
1958	KVILKPDKTTITEPH	ubiquitination	[4, 6]
1993	LILADYGKKNNVNVA	ubiquitination	[1, 2, 7]
1994	ILADYGKKNNVNVAS	ubiquitination	[1, 3, 7]
2031	QQIAEIEKQTKEQSQ	ubiquitination	[1, 3, 7]
2034	AEIEKQTKEQSQLTA	ubiquitination	[1, 2, 3, 5, 7, 8]
2049	TQTRTVNKHGDEIIT	ubiquitination	[1, 3, 7]
2070	ETQTFSSKTEWRVRA	ubiquitination	[3, 5]
2098	YVSSDDIKETGYTYI	ubiquitination	[3]
2108	GYTYILPKNVLKKFI	ubiquitination	[3, 7]
2112	ILPKNVLKKFICISD	ubiquitination	[3]
2113	LPKNVLKKFICISDL	ubiquitination	[3]
2140	PPDNPQVKEIRCIVM	ubiquitination	[1, 2, 3, 5, 7, 11]
2249	TDKGNNPKGYLPSHY	ubiquitination	[3]
2293	VRHDPNMKYELQLAN	ubiquitination	[1, 2, 3, 5, 7, 8]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [8] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [9] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [10] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [11] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [12] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 

Functional Description

 Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site. 

Sequence Annotation

 DOMAIN 2099 2233 MPN.
 REGION 812 1303 Reverse transcriptase homology domain.
 REGION 1304 1577 Linker.
 REGION 1513 1526 Important for branch point selection (By
 REGION 1581 1752 Restriction endonuclease homology domain.
 REGION 1669 2034 Involved in interaction with pre-mRNA 5'
 REGION 1767 2020 RNase H homology domain.
 REGION 2301 2335 Required for interaction with EFTUD2 and
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 859 859 Phosphoserine.
 MOD_RES 1318 1318 Phosphothreonine (By similarity).
 MOD_RES 1463 1463 N6-acetyllysine.
 MOD_RES 2042 2042 Phosphothreonine (By similarity).  

Keyword

 3D-structure; Acetylation; Complete proteome; Direct protein sequencing; Disease mutation; mRNA processing; mRNA splicing; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Retinitis pigmentosa; Ribonucleoprotein; RNA-binding; Spliceosome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 2335 AA 

Protein Sequence

Gene Ontology

 GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
 GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005682; C:U5 snRNP; TAS:ProtInc.
 GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
 GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB. 

Interpro

 IPR000555; JAB1_Mov34_MPN_PAD1.
 IPR012591; Pre-mRNA-splicing_factor-8.
 IPR012984; PRO_C.
 IPR012592; PROCN.
 IPR021983; PRP8_domainIV.
 IPR019581; Prp8_U5-snRNA-bd.
 IPR019580; Prp8_U6-snRNA-bd.
 IPR019582; RRM_spliceosomal_PrP8. 

Pfam

 PF01398; JAB
 PF08082; PRO8NT
 PF08083; PROCN
 PF08084; PROCT
 PF12134; PRP8_domainIV
 PF10598; RRM_4
 PF10597; U5_2-snRNA_bdg
 PF10596; U6-snRNA_bdg 

SMART

 SM00232; JAB_MPN 

PROSITE

  

PRINTS